Squamous cell carcinomas (SCCs) are the most common form of human solid tumors and major cause of cancer lethality. Squamous cell carcinomas are notoriously resistant to conventional and targeted drug treatments.
Notch signaling plays a pivotal role in diverse developmental, physiological and pathological processes. Among the four known Notch receptors, Notch1 plays the most significant role in squamous cell differentiation. Recent whole genome sequencing studies identified recurrent loss-of-function mutations of the Notch1 gene in head and neck, cutaneous and lung SCCs, consistent with the tumor suppressing function that Notch1 activation can play in this tumor type. Control of Notch1 activity has been highly studied at the level of receptor processing and activation, while surprisingly little is known on direct transcription control of the Notch1 gene.